tbuckley/cabot-search huggingface dataset:
The risks of first hepatic decompensation and HCC remain constant during long-term follow-up and can be stratified by a one-time assessment after HCV-cure
Authors: Georg Semmler, Sonia Alonso Lopez, Monica Pons, Sabela Lens, Elton Dajti, Marie Griemsmann, Alberto Zanetto, Lukas Burghart, Stephanie Hametner-Schreil, Lukas Hartl, Adriana Ahumada, Sergio Rodriguez-Tajes, Paola Zanaga, Michael Schwarz, Clara Uson, Mathias Jachs, Anna Pocurull, Maria Luisa Manzano Alonso, Dominik Ecker, Daniel Riado, Beatriz Mateos Muñoz, Michael Gschwantler, Francesco Paolo Russo, Francesco Azzaroli, Benjamin Maasoumy, Thomas Reiberger, Xavier Forns, Joan Genesca, Rafael Bañares, Mattias Mandorfer
Journal: Journal of Hepatology (2023)
A3907, a systemic ASBT inhibitor, improves cholestasis in mice by inhibiting multi-organ bile acid transport and shows translational relevance to human
Authors: Francisco J. Caballero, Pedro Miguel Rodrigues, Aloña Agirre Lizaso, Paula Olaizola, Laura Izquierdo-Sánchez, María Jesús Perugorria, Luis Bujanda, Bo Angelin, Sara Straniero, Anna Wallebäck, Ingemar Starke, Per-Göran Gillberg, Ellen Strängberg, Fredrik Wangsell, Jan Mattsson, Henrik B. Hansen, Erik Lindström, Peter Akerblad, Jesus Maria Banales
Journal: Journal of Hepatology (2023)
Pyroptotic MAITs link microbial translocation with severity of alcohol-related liver disease
Authors: Li-Ping Zhang, Hui-Fang Wang, Xing-Ran Zhai, Chun-Bao Zhou, Jin-Hong Yuan, Ye-Nv Ma, Zeng-Tao Yao, Shuo Huang, Wei-Zhe Li, Yan-Mei Jiao, Fu-Sheng Wang, Zhengsheng Zou, Ji-Yuan Zhang, Qing-Lei Zeng
Journal: Journal of Hepatology (2023)
Glial transcriptional changes in experimental HE arise early and show similarities with established neuroinflammatory disorders
Authors: Wouter Claeys, Lien Van Hoecke, Clint De Nolf, Hannah Lernout, Griet Van Imschoot, Elien Van Wonterghem, Daan Verhaege, Anja Geerts, Christophe Van Steenkiste, Roosmarijn Vandenbroucke
Journal: Journal of Hepatology (2023)
Offspring of obese mothers have a higher risk for hepatocellular carcinoma through the transmission of an altered gut microbiome
Authors: Beat Moeckli, Vaihere Delaune, Benoit Gilbert, Andrea Peloso, Graziano Oldani, Sofia El Hajji, Florence Slits, Quentin Gex, Stéphanie Lacotte, Christian Toso
Journal: Journal of Hepatology (2023)
A prospective study of hepatic fibrosis evaluation in an alcohol withdrawal unit of an university hospital center: role of FIB-4 and elastometry. Fibr’addict study
Authors: Armand Abergel, Benjamin Buchard, Leon Muti, Dominique Boulier, Maud Leautaud, Brigitte Chanteranne, Carine Nicolas, Sylvie Massoulier, Frédéric Faure, Anne Audrey Schmitt-Dischamp, Georges Brousse
Journal: Journal of Hepatology (2023)
Prospective direct comparisons of four widespread non-invasive fibrosis tests (NITs) in outpatients with type-2 diabetes (T2D) using EPoS histological staging as reference
Authors: Olivier Deckmyn, Dominique Valla, Valentina Peta, Angélique Brzustowski, Valérie Paradis, Pierre Bedossa, Castera Laurent, Stanislas Pol, Raluca Pais, Vlad Ratziu, Dominique Thabut, Jean-François Gautier, Thierry Poynard
Journal: Journal of Hepatology (2023)
Safety, pharmacokinetics and antiviral efficacy of freethiadine, a novel capsid assembly modulator, in healthy volunteers and patients with chronic hepatitis B virus infection
Authors: Yanhua Ding, Xiaojiao Li, Jia Xu, Jixuan Sun, Yingjun Zhang, Jing Zhu, Yujie Chen, Lin Luo, Qingyun Ren, Yunfu Chen, Junqi Niu
Journal: Journal of Hepatology (2023)
Stanozolol-induced liver injury: a peculiar biochemical profile in a series of thirteen cases
Authors: Vinicius Nunes, Isadora Almeida, Maria Carolina Campos, Bárbara Freire, Marcelo Silva, Raymundo Parana Filho, Fernando Bessone, Nélia Hernandez, Eduardo Cancado, Maria Schinoni
Journal: Journal of Hepatology (2023)
Effect of fibrinogen substitution in hypofibrinogenaemic CTP class C patients on viscoelastic coagulation tests
Authors: Moritz Tobiasch, Anna Tobiasch, Volker Schäfer, Johannes Bösch, Mirjam Bachler, Philipp Lichtenberger, Heinz Zoller, Dietmar Fries
Journal: Journal of Hepatology (2023)
Efficacy and safety of branched-chain amino acids supplementation on muscle cramps in patients with cirrhosis: a randomized double-blinded controlled trial
Authors: Tanongsak Chinaroonchai, Thanapat Atthakitmongkol, Supot Nimanong, Watcharasak Chotiyaputta, Phunchai Charatcharoenwitthaya, Tawesak Tanwandee, Siwaporn Chainuvati
Journal: Journal of Hepatology (2023)
Multimodal integrative genomics and pathology analyses in neoadjuvant nivolumab treatment for borderline resectable HCC
Authors: Tan-to Cheung, Daniel Ho, Shirley Lyu, Qingyang Zhang, Yu Tsui, Tiffany Yu, Karen Sze, Joyce Lee, Vince Lau, Yin-Lun Chu, Simon Tsang, Wong She, Roland Leung, Thomas Yau, Irene Oi-Lin Ng
Journal: Journal of Hepatology (2023)
Recently validated non-invasive tests for liver fibrosis assessment have great performance in identifying NASH patients at risk for decompensation
Authors: Vlad Taru, Madalina Gabriela Taru, Bobe Petrushev, Rusu Ioana, Horia Stefanescu, Andreea Fodor, Mina Dana Ignat, Fischer Petra, Oana Nicoara-Farcau, Monica Platon, Bogdan Procopet
Journal: Journal of Hepatology (2023)
Tripartite Motif Protein 32 Facilitates Cell Growth and Migration via Degradation of Abl-Interactor 2
Authors: Satoshi Kano, Naoto Miyajima, Satoshi Fukuda, Shigetsugu Hatakeyama
Journal: Cancer Research (2008)

Abstract Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs. [Cancer Res 2008;68(14):5572–80]
Characteristics and outcomes of patients with chronic myeloid leukemia and <scp>T315I</scp> mutation treated in the pre‐ and post‐ponatinib era
Authors: Fadi G. Haddad, Koji Sasaki, Aram Bidikian, Ghayas C. Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J. Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P. Patel, Rashmi Kanagal‐Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2023)

Abstract Patients with chronic myeloid leukemia (CML) and T315I mutation generally have a poor prognosis. Their outcome in the post‐ponatinib era remains unclear. We reviewed patients with CML in chronic (CP) or accelerated phase (AP) who developed a T315I mutation between March 15, 2004, and July 26, 2022. Patients were divided into CP, AP, or blastic phase (BP) at the time of mutation detection. Overall survival (OS) was defined from the time of mutation detection to the date of death or last follow‐up. We identified a total of 107 patients: 54 (51%) in CP, 14 (13%) in AP, and 39 (36%) in BP. One hundred and two patients received subsequent therapy after the T315I mutation was detected. At a median follow‐up of 75 months (95% CI, 41–110), the median OS was 49 months (95% CI, 26–73) and the 5‐year OS rate was 44%. Patients who were in CML‐CP at the time of mutation detection had better survival compared with those in AP or BP, with a median OS of 132, 31, and 6 months, and 5‐year OS rates of 70%, 37%, and 10%, respectively ( p &lt; .001). Patients with CML‐CP treated with ponatinib and/or asciminib had a 5‐year OS of 77% compared with 50% in those who received other treatments (chemotherapy, second‐generation tyrosine kinase inhibitors, homoharringtonine, and investigational drugs) ( p = .14). In summary, patients with CML‐CP at the time of T315I mutation detection may have a relatively indolent disease course with a long‐term OS of 70%. Treatment with third‐generation tyrosine kinase inhibitors seemed to improve survival in patients with CML‐CP.
The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
Authors: Marta Sampietro, Valeria Cassina, Domenico Salerno, Federica Barbaglio, Enrico Buglione, Claudia Adriana Marrano, Riccardo Campanile, Lydia Scarfò, Doreen Biedenweg, Bob Fregin, Moreno Zamai, Alfonsa Díaz Torres, Veronica Labrador Cantarero, Paolo Ghia, Oliver Otto, Francesco Mantegazza, Valeria R. Caiolfa, Cristina Scielzo
Journal: HemaSphere (2023)

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an intense trafficking of the leukemic cells between the peripheral blood and lymphoid tissues. It is known that the ability of lymphocytes to recirculate strongly depends on their capability to rapidly rearrange their cytoskeleton and adapt to external cues; however, little is known about the differences occurring between CLL and healthy B cells during these processes. To investigate this point, we applied a single-cell optical (super resolution microscopy) and nanomechanical approaches (atomic force microscopy, real-time deformability cytometry) to both CLL and healthy B lymphocytes and compared their behavior. We demonstrated that CLL cells have a specific actomyosin complex organization and altered mechanical properties in comparison to their healthy counterpart. To evaluate the clinical relevance of our findings, we treated the cells in vitro with the Bruton's tyrosine kinase inhibitors and we found for the first time that the drug restores the CLL cells mechanical properties to a healthy phenotype and activates the actomyosin complex. We further validated these results in vivo on CLL cells isolated from patients undergoing ibrutinib treatment. Our results suggest that CLL cells' mechanical properties are linked to their actin cytoskeleton organization and might be involved in novel mechanisms of drug resistance, thus becoming a new potential therapeutic target aiming at the normalization of the mechanical fingerprints of the leukemic cells.
Helminths revive to survive
Authors: John R. Grainger, Rufus H. Daw
Journal: The Journal of Experimental Medicine (2022)

Helminth parasites are well known to have co-evolved a diverse arsenal of immunomodulatory factors to aid their persistence following infection. In this issue, Karo-Atar et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212311) demonstrate that products released by the gut-dwelling helminth Heligmosomoides polygyrus barkeri modify intestinal stem cells into a “revival” state, which is associated with a loss of helminth-expelling secretory cell types from the epithelium.
A cohort study found a high risk of end-stage kidney disease associated with acromegaly
Authors: Sangmo Hong, Kyung-Soo Kim, Kyungdo Han, Cheol-Young Park
Journal: Kidney International (2023)

Acromegaly is a chronic systemic disease caused by excess levels of growth hormone and insulin-like growth factor-1 and is associated with numerous complications. Significantly, there is a lack of longitudinal data on kidney complications in patients with acromegaly. As such, we investigated the risk of end-stage kidney disease (ESKD) (stage 5D, 5T) in these patients with nationwide data obtained from the National Health Information Database of the National Health Insurance Service in Republic of Korea. A retrospective cohort study was conducted of 2.187 patients with acromegaly and 10,935 age- and sex-matched (1:5) control subjects without acromegaly over a mean follow-up period of 6.51 years. The study outcomes were analyzed using Cox proportional hazards regression analysis controlling for age, sex, household income, residential area, type 2 diabetes, hypertension, dyslipidemia, urolithiasis, congestive heart failure, myocardial infarction, stroke, and atrial fibrillation. The incidence (per 1,000 person-years) ESKD was 2.00 among patients with acromegaly but only 0.46 among controls, (hazard ratio 4.35 (95% confidence interval 2.63-7.20)) implicating a significantly higher risk. After adjustment for covariates, the risk of ESKD (2.36 (1.36-4.12)) was still significantly higher in patients with acromegaly than that in controls. Among the covariates, diabetes and hypertension were significant facilitators between acromegaly and ESKD in mediation analysis. Pituitary surgery and somatostatin analogues did not significantly change these associations. Thus, acromegaly may be linked with a higher risk for ESKD both independently and through mediators such as diabetes and hypertension.
Systemic complement activation influences outcomes after allogeneic hematopoietic cell transplantation: A prospective <scp>French</scp> multicenter trial
Authors: Anne Béatrice Notarantonio, Maud D'aveni‐Piney, Simona Pagliuca, Yayha Ashraf, Jacques‐Emanuel Galimard, Aliénor Xhaard, Ambroise Marçais, Felipe Suarez, Eolia Brissot, Pierre Feugier, Saik Urien, Naim Bouazza, Sébastien Jacquelin, Tchao Meatchi, Patrick Bruneval, Véronique Frémeaux‐Bacchi, Régis Peffault De Latour, Olivier Hermine, Marie Agnès Durey‐Dragon, Marie‐Thérèse Rubio
Journal: American Journal of Hematology (2023)

Complement activation has shown a role in murine models of graft-versus-host disease (GVHD) and in endothelial complications after allogeneic hematopoietic cell transplantation (allo-HSCT). However, its impact on post-transplant outcomes has not been so far fully elucidated. Here, we conducted a prospective multicentric trial (NCT01520623) performing serial measurements of complement proteins, regulators, and CH50 activity for 12 weeks after allo-HSCT in 85 patients receiving a myeloablative conditioning (MAC) regimen for various hematological malignancies. Twenty-six out of 85 patients showed an "activated" complement profile through the classical/lectin pathway, defined as a post-transplant decline of C3/C4 and CH50 activity. Time-dependent Cox regression models demonstrated that complement activation within the first weeks after allo-HSCT was associated with increased non-relapse mortality (hazard ratio [HR]: 3.69, 95% confident interval [CI]: 1.55-8.78, p = .003) and poorer overall survival (HR: 2.72, 95% CI: 1.37-5.39, p = .004) due to increased incidence of grade II-IV acute GVHD and in particular gastrointestinal (GI) GVHD (HR: 36.8, 95% CI: 12.4-109.1, p < .001), higher incidences of thrombotic microangiopathy (HR: 8.58, 95% CI: 2.16-34.08, p = .0022), capillary leak syndrome (HR: 7.36, 95% CI: 2.51-21.66, p = .00028), post-engraftment bacterial infections (HR: 2.37, 95% CI: 1.22-4.63, p = .0108), and EBV reactivation (HR: 3.33, 95% CI: 1.31-8.45, p = .0112). Through specific immune staining, we showed the correlation of deposition of C1q, C3d, C4d, and of C5b9 components on endothelial cells in GI GVHD lesions with the histological grade of GVHD. Altogether these findings define the epidemiology and the clinical impact of complement classical/lectin pathway activation after MAC regimens and provide a rational for the use of complement inhibitory therapeutics in a post-allo-HSCT setting.
Glucose-responsive, antioxidative HA-PBA-FA/EN106 hydrogel enhanced diabetic wound healing through modulation of FEM1b-FNIP1 axis and promoting angiogenesis
Authors: Wenqian Zhang, Kangkang Zha, Yuan Xiong, Weixian Hu, Lang Chen, Ze Lin, Chenyan Yu, Wu Zhou, Faqi Cao, Hankun Hu, Bobin Mi, Guohui Liu
Journal: Bioactive Materials (2023)

The diabetic wounds remain to be unsettled clinically, with chronic wounds characterized by drug-resistant bacterial infections, compromised angiogenesis and oxidative damage to the microenvironment. To ameliorate oxidative stress and applying antioxidant treatment in the wound site, we explore the function of folliculin-interacting protein 1 (FNIP1), a mitochondrial gatekeeper protein works to alter mitochondrial morphology, reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation. And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment. To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites, a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing. Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid (HA) and phenylboronic acid (PBA), the hydrogel is able to realize a glucose-responsive release of drugs. Fulvic acid (FA) is added in the hydrogel, which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities. Moreover, the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation. These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel, which may provide a promising strategy for chronic diabetic wound repair.
Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy
Authors: Yanyu Jiang, Shuaishuai Ni, Biying Xiao, Lijun Jia
Journal: Acta Pharmaceutica Sinica B (2023)

Ubiquitin (Ub) and ubiquitin-like (Ubl) pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/inactivated. To date, >600 associated enzymes have been reported that comprise a hierarchical task network (e.g., E1-E2-E3 cascade enzymatic reaction and deubiquitination) to modulate substrates, including enormous oncoproteins and tumor-suppressive proteins. Several strategies, such as classical biochemical approaches, multiomics, and clinical sample analysis, were combined to elucidate the functional relations between these enzymes and tumors. In this regard, the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl pathways. Correspondingly, emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed essential. In the present review, we summarize and discuss the functions, clinical significance, and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug discovery. In particular, multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer therapy. The present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.
Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration
Authors: Qinghua Li, Huijuan Song, Shuangyang Li, Pengbo Hu, Chuangnian Zhang, Ju Zhang, Zujian Feng, Deling Kong, Weiwei Wang, Pingsheng Huang
Journal: Bioactive Materials (2023)

Excessive reactive oxygen species (ROS) at severe burn injury sites may promote metabolic reprogramming of macrophages to induce a deteriorative and uncontrolled inflammation cycle, leading to delayed wound healing and regeneration. Here, a novel bioactive, anti-fouling, flexible polyzwitterionic hydrogel encapsulated with epigallocatechin gallate (EGCG)-copper (Cu) capsules (termed as [email protected]gel) is engineered for burn wound management, which is dedicated to synergistically exerting ROS-scavenging, immune metabolic regulation and pro-angiogenic effects. [email protected]gel can scavenge ROS to normalize intracellular redox homeostasis, effectively relieving oxidative damages and blocking proinflammatory signal transduction. Importantly, EGCG-Cu can inhibit the activity of hexokinase and phosphofructokinase, alleviate accumulation of pyruvate and convert it to acetyl coenzyme A (CoA), whereby inhibits glycolysis and normalizes tricarboxylic acid (TCA) cycle. Additionally, metabolic reprogramming of macrophages by EGCG-Cu downregulates M1-type polarization and the expression of proinflammatory cytokines both in vitro and in vivo. Meanwhile, copper ions (Cu2+) released from the hydrogel facilitate angiogenesis. [email protected]gel significantly accelerates the healing of severe burn wound via promoting wound closure, weakening tissue-damaging inflammatory responses and enhancing the remodeling of pathological structure. Overall, this study demonstrates the great potential of bioactive hydrogel dressing in treating burn wounds without unnecessary secondary damage to newly formed skin, and highlights the importance of immunometabolism modulation in tissue repair and regeneration.
The association between <i>Staphylococcus aureus</i> colonization on cheek skin at 2 months and subsequent atopic dermatitis in a prospective birth cohort
Authors: Maria Rasmussen Rinnov, Trine Gerner, Anne-Sofie Halling, Mie Sylow Liljendahl, Nina Haarup Ravn, Mette Hjorslev Knudgaard, Simon Trautner, Lone Skov, Simon Francis Thomsen, Alexander Egeberg, Ivone Jakasa, Sanja Kezic, Andreas Petersen, Anders Rhod Larsen, Casper Dam-Nielsen, Jens Otto Jarløv, Jacob P Thyssen
Journal: British Journal of Dermatology (2023)

Staphylococcus aureus may worsen already established atopic dermatitis (AD), but its primary role in the aetiopathogenesis and severity of AD is unclear.To compare the prevalence of S. aureus colonization in early infancy in children who developed AD during the first 2 years of life with children who did not.In this prospective birth cohort study, which included 450 infants, we analysed bacterial swabs collected from cheek skin at 0 and 2 months of age. The development of AD, and its severity, was diagnosed by a physician and monitored prospectively for 2 years. Information on parental atopy, filaggrin gene mutation status and use of antibiotics and emollients was included in the analyses.At birth, the occurrence of S. aureus colonization was similar in infants who developed subsequent AD and those who did not. At 2 months of age, S. aureus colonization was more common in children who later developed AD (adjusted hazard ratio 1.97, 95% confidence interval 1.21-3.19; P = 0.006). No association was found between S. aureus colonization and AD severity or age at onset.It remains unknown whether colonization with S. aureus may directly increase the risk of AD, or whether it should be considered as secondary to skin barrier impairment or a skewed immune activity, but according to our findings, S. aureus colonization is more commonly increased at 2 months of age in children who later developed AD.